(A) crucial role of WW45 in developing epithelial tissues in the mouseWW45 유전자의 마우스 상피조직에서의 세포주기 및 분화 조절 기능에 관한 연구

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The role and molecular mechanisms of a new Hippo signaling pathway are not fully understood in mammals. Here, we generated mice lacking WW45 and reveal a crucial role of WW45 in cell-cycle exit for epithelial terminal differentiation. Many organs in mutant embryos displayed hyperplasia accompanied by defects of terminal differentiation of epithelial cells owing to impairment of proliferation stop of epithelial cells rather than intrinsic acceleration of proliferation during differentiation. Importantly, MST1 signaling pathway is specifically activated in only differentiating epithelial cells. We also found that WW45 is required for MST1 activation and translocation to the nucleus for subsequent LATS1/2 activation, which then phosphorylate serine 127 of YAP upon differentiation signal. This phosphorylated YAP translocates from the nucleus into the cytoplasm, thereby resulting in cell-cycle exit and terminal differentiation. Collectively, these data provide compelling evidence that WW45 is a key mediator of MST1 signaling in the coordinate coupling of proliferation stop with terminal differentiation for proper epithelial tissue development in mammals.
Advisors
Llim, Dae-Sikresearcher임대식researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2008
Identifier
310402/325007  / 020035239
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2008.2, [ vii, 97 p. ]

Keywords

cell cycle exit; epithelial differentiation; hyperplasia; knockout mouse; tumorigenesis; 세포주기; 상피 분화; 과증식; 유전자 적중 마우스; 종양; cell cycle exit; epithelial differentiation; hyperplasia; knockout mouse; tumorigenesis; 세포주기; 상피 분화; 과증식; 유전자 적중 마우스; 종양

URI
http://hdl.handle.net/10203/27670
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=310402&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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